This competing continuation of K05DA17918 is submitted in response to PA-09-076 and requests 5 additional years of support to provide protected time for the PI to continue a successful preclinical research program on the behavioral pharmacology of opioids and other drugs and to mentor students and other young investigators in the area of drug abuse. Progress on the original aims of this grant was as follows: 1) increased NIH support for the PI, his mentees, and collaborators;2) made significant progress in research projects on the behavioral pharmacology of opioids and other drugs of abuse;3) significantly increased drug abuse research and training activities at UTHSCSA;4) led the effort to expand and renovate animal facilities for behavioral research on drug abuse;and 5) contributed to the successful career development of student and junior faculty mentees. The current grant comprises 5 specific aims. Aim 1 continues a 23-year research program on opioid dependence and withdrawal with a new focus on drug combinations. Aim 2 builds on compelling new data showing that chronic opioid treatment and its discontinuation dramatically alter delay discounting, an often used measure of an important aspect of impulsivity, delay discounting. Aim 3 continues and expands a successful collaboration with several investigators and explores the effects of food restriction and of eating high fat food on behavioral, neurochemical, and other effects of drugs acting on serotonin and dopamine systems. Aim 4 continues an active mentoring program (>25% effort) of students and young investigators, and Aim 5 promotes further growth in drug abuse research and training activities at UTHSCSA, including preparation of T32 and multi-investigator research applications. Prior support under the K mechanism has allowed the PI to continue and expand his research efforts as well as the research programs of his collaborators. Continued support under this K award will allow the PI to devote at least 75% of his effort to research and mentoring in drug abuse. PUBLIC HEALTH RELEVANCE: Despite the importance of opioids for treating pain, they are not effective in many patients, and their clinical use is limited by concerns about abuse and dependence;while impulsivity and drug abuse often covary, it is not clear whether impulsivity is a risk or cause of drug abuse and little is known about how drug use, especially chronic drug use, impacts impulsivity. Food and drugs can affect the same reward mechanism in brain, although the impact of feeding conditions on drug effects is poorly understood. Research conducted under this Senior Scientist Award examines three different drug abuse related questions: 1) can drugs of abuse that are used to treat pain be taken together without increasing their abuse;2) can drugs of abuse increase impulsivity when they are taken or when they are no longer taken;and 3) can drugs of abuse have effects that depend on how much and what you eat?